• The Korean Journal of Physiology and Pharmacology
• /
• 제26권5호
• /
• pp.377-387
• /
• 2022

Benzimidazole anthelmintic agents have been recently repurposed to overcome cancers resistant to conventional therapies. To evaluate the anti-cancer effects of benzimidazole on resistant cells, various cell death pathways were investigated in 5-fluorouracil-resistant colorectal cancer cells. The viability of wild-type and 5-fluorouracil-resistant SNU-C5 colorectal cancer cells was assayed, followed by Western blotting. Flow cytometry assays for cell death and cell cycle was also performed to analyze the anti-cancer effects of benzimidazole. When compared with albendazole, fenbendazole showed higher susceptibility to 5-fluorouracil-resistant SNU-C5 cells and was used in subsequent experiments. Flow cytometry revealed that fenbendazole significantly induces apoptosis as well as cell cycle arrest at G2/M phase on both cells. When compared with wild-type SNU-C5 cells, 5-fluorouracil-resistant SNU-C5 cells showed reduced autophagy, increased ferroptosis and ferroptosis-augmented apoptosis, and less activation of caspase-8 and p53. These results suggest that fenbendazole may be a potential alternative treatment in 5-fluorouracil-resistant cancer cells, and the anticancer activity of fenbendazole does not require p53 in 5-fluorouracil-resistant SNU-C5 cells.

• 생명과학회지
• /
• 제34권6호
• /
• pp.418-425
• /
• 2024

고형암은 여러 세포 유형의 이질적인 집단으로 구성되며, 암줄기세포는 자가 재생과 분화의 특성을 가지고 있다. 암줄기세포에서는 자가재생을 조절하는 줄기세포 신호전달체계가 과도하게 활성화되어 있어 암줄기세포는 암세포의 증식과 암 진행에 중요하다. 암줄기세포의 정의는 급성골수성백혈병에 의해 처음 제안되었으며, 다양한 연구를 통해 세포 표면 표지 발현에 따라 암 줄기세포를 분류할 수 있게 되었다. 또한, 암줄기세포는 종양 미세환경에서 잠재력을 보존하고 있고, 다양한 종양 미세환경 세포 유형은 정지 상태의 암줄기 세포를 유지하고 암 성장의 조절자 역할을 한다. 현재 사용되는 암 치료 방법은 증식성 세포를 표적으로 하기 때문에 치료에, 저항성을 가지는 휴지기 상태의 암 줄기세포는 재발이나 전이의 위험을 증가시키며, 종양 미세환경의 다양한 신호전달체계는 혈관계와 세포 외 기질을 리모델링함으로써 종양 지지 환경으로의 변화를 유도한다. 따라서, 암을 효과적으로 치료하려면 암줄기세포와 종양 미세환경을 표적 치료해야 하며, 종양 미세환경이 어떻게 면역 반응의 재프로그램을 유도하여 암의 성장, 면역 저항성 및 전이를 촉진하는지 이해하는 것이 중요하다. 따라서 본 총설을 통해 종양 미세환경에서 면역억제를 강화할 수 있는 세포 및 분자 메커니즘에 대한 현재 및 새로운 개념을 요약하고자 한다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권15호
• /
• pp.6349-6352
• /
• 2014

The present study was undertaken to determine the roles of insulin in the growth of transplanted breast cancer in nude mice, and the proliferation and migration of MCF-7 human breast cancer cells and assess its influence on downstream signaling pathways. In a xenograft mouse model with injection of MCF-7 human breast cancer cells, tumor size was measured every other day. The insulin level and insulin receptor (IR) were increased in the breast cancer patient tissues. Insulin injected subcutaneously around the tumor site in mice caused increase in the size and weight of tumor masses, and promoted proliferation and migration of MCF-7 cells. The effects of insulin on the increase in the proliferation and migration of MCF-7 human breast cancer cells were abolished by pretreatment with the extracellular regulated kinase (ERK) inhibitor PD98059. Insulin increased the phosphorylation of ERK in the MCF-7 cells. These results indicate that insulin promotes the growth of breast cancer in nude mice, and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway.

• Molecules and Cells
• /
• 제28권1호
• /
• pp.7-12
• /
• 2009

Gliomas, much like other cancers, are composed of a heterogeneous mix of neoplastic and non-neoplastic cells that include both native and recruited cells. There is extensive diversity among the tumor cells, with differing capacity for In vitro and in vivo growth, a property intimately linked to the cell's differentiation status. Those cells that are undifferentiated, self-renewing, with the capacity for developing tumors (tumorigenic) cells are designated by some as cancer stem cells, because of the stem-like properties. These cells may be a critical therapeutic target. However the exact identity and cell(s) of origin of the socalled glioma cancer stem cell remain elusive. Here we review the current understanding of glioma cancer stem cell biology.

• Preventive Nutrition and Food Science
• /
• 제4권2호
• /
• pp.107-112
• /
• 1999

Effect of solvent extracts and juice supernatants from kimchis on the growth of various human cancer cells was studied, comparing with the actions on the normal cells. Inhibitory effect of kimchi extracts on[3H] thymidine incorporation n cancer cells was also investigated. The methanol extract, hexane extract and methanol soluble fraction (MSF) of 3-week fermented kimchi did not have growth inhibitory effect on Ac2F rat normal liver cells at the concentrations of 0.5~2%. However, marked decrease in the growth of AGS human gastric cancer cells was shown by the treatment of those extacts. The juice from the kimchi samples also suppressed the growth of K-562 human leukemia cells and MG-63 human osteosarcoma cells. Especially, the juice of 3-week fermented kimchi exhibited the strong growth inhibitory effect in MG-63 human osteosarcoma cells. At the photomicrographs, growth inhibition and morphological change of the cells treated with kimchi juice were observed. And the solvent extracts of 3-week fermented kimchi suppressed the growth of cancer morethan the extracts or juices from fresh and 6-week fermented kimchi. When AGS human gastric cancer cels were treated with the extracts of 3-week fermented kimchi, [3H] thymidine incorporation in the cells also decreased. These results showed that kimchi extracts and juices had growth inhibitory effects on human osteosarcoma, leukemia and gastric cancer cells, but had no toxicity to the normal cells. We suggest that kimchi might have anticancer effect in part due to inhibition of the growth and DNA synthesis of cancer cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권20호
• /
• pp.8549-8556
• /
• 2014

Head and neck squamous cell carcinoma (HNSCC) is one of the world top ten most common cancers with its highest occurrence in the Indian subcontinent and different aggressive and etiological behavioural patterns. The scenario is only getting worst with the 5 year survival rates dropping to 50%, persistent treatment failures and frequent cases of relapse/recurrence. One of the major reasons for these failures is the presence of cancer stem cells (CSCs), a small population of cancer cells that are highly tumourigenic, capable of self-renewal and have the ability to differentiate into cells that constitute the bulk of tumours. Notably, recent evidence suggests that cancer stem cells are especially resistant to conventional therapy and are the "drivers" of local recurrence and metastatic spread. Specific markers for this population have been investigated in HNSCC in the hope of developing a deeper understanding of their role in oral cancer pathogenesis, elucidating novel biomarkers for early diagnosis and newer therapeutic strategies. This review covers the fundamental relevance of almost all the CSC biomarkers established to date with a special emphasis on their impact in the process of oral tumourigenesis and their potential role in improving the diagnosis, prognosis and treatment of OSCC patients.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권8호
• /
• pp.4675-4678
• /
• 2013

The aim of this study was to detect the expression of miR196a, miR146a, miR27a and miR200a in patients with colon cancer, and investigate the effect of miR27a expression on proliferation and invasion in colonic cancer cells. RT-PCR was employed to detect the expression levels in colon cancers. Then, colon cancer cells were cultured and transfected with 100 nM of miR27a mimics (80 nmol/L) or 80 nM miR27a inhibitors (80 nmol/L) in 24-well plates. Proliferation and invasion of colonic cancer cells were then determined by CCK-8 and Transwell assays, respectively. Our data showed miR27a to be high-expressed in patients with colon cancer. In addition, proliferation and invasion in the miR27a mimic group were significantly higher than in the control group and negative group (P<0.05), while, proliferation and invasion in the miR27a inhibitor group were obviously lowered (P<0.05). In conclusion, high expression of miR27a may play an important role in enhancing proliferation and invasion of colon cancer cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권3호
• /
• pp.1119-1122
• /
• 2016

Background: Punica granatum (PG) has been demonstrated to possess antitumor effects on various types of cancer cells. In this study, we determined antiproliferative properties of a seed extract of PG (PSE) from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate seeds was prepared. Total phenolic content (TPC) and total flavonoid content (TFC) were assessed by colorimetric assays. Antioxidant activity was determined with reference to DPPH radical scavenging activity. The cytotoxicity of different doses of PSE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell carcinoma), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all studied cancer cells, PSE reduced the cell viability to values below 23%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, SKOV3 ovarian cancer cells were the most responsive to antiproliferative effects of PSE with a maximum mean growth inhibition of 86.8% vs. 82.8%, 81.4% and 80.0% in MCF-7, PC-3 and A549 cells, respectively. Conclusions: Low doses of PSE exert potent antiproliferative effects on different human cancer cells SKOV3 ovarian cancer cells as most and A549 cells ar least responsive regarding cytotoxic effects. However, the mechanisms of action need to be addressed.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권1호
• /
• pp.169-174
• /
• 2015

Cervical cancer (CxCa) is the most common cancer in women and a prominent cause of cancer mortality worldwide. The primary cause of CxCa is human papillomavirus (HPV). Radiation therapy and chemotherapy have been used as standard treatments, but they have undesirable side effects for patients. It was reported that gallic acid has antioxidant, antimicrobial, and anticancer activities. Gold nanoparticles are currently being used in medicine as biosensors and drug delivery agents. This study aimed to develop a drug delivery agent using gold nanoparticles conjugated with gallic acid. The study was performed in uninfected (C33A) cervical cancer cells, cervical cancer cells infected with HPV type 16 (CaSki) or 18 (HeLa), and normal Vero kidney cells. The results showed that GA inhibited the proliferation of cancer cells by inducing apoptosis. To enhance the efficacy of this anticancer activity, 15-nm spherical gold nanoparticles (GNPs) were used to deliver GA to cancer cells. The GNPs-GA complex had a reduced ability compared to unmodified GA to inhibit the growth of CxCa cells. It was interesting that high-concentration ($150{\mu}M$) GNPs-GA was not toxic to normal cells, whereas GA alone was cytotoxic. In conclusion, GNPs-GA could inhibit CxCa cell proliferation less efficiently than GA, but it was not cytotoxic to normal cells. Thus, gold nanoparticles have the potential to be used as phytochemical delivery agents for alternative cancer treatment to reduce the side effects of radiotherapy and chemotherapy.

• Journal of Microbiology and Biotechnology
• /
• 제28권6호
• /
• pp.874-882
• /
• 2018

Curcumin is known to possess various biological functions, including anti-inflammatory, anti-oxidative, and anti-cancer activities. Natural killer (NK) cells are large lymphocytes that directly kill cancer cells. However, many aggressive cancers, including breast cancer, were reported to escape the successful killing of NK cells in a tumor microenvironment. In this study, we investigated the anti-cancer effect of curcumin in coculture of human breast carcinoma MDA-MB-231 and NK (NK-92) cells. We found that curcumin had an immune-stimulatory effect on NK-92 by increasing the surface expression of the $CD16^+$ and $CD56^{dim}$ population of NK-92. We confirmed that the cytotoxic effect of NK-92 on MDA-MB-231 was significantly enhanced in the presence of curcumin, which was highly associated with the activation of Stat4 and Stat5 proteins in NK-92. Finally, this improved anticancer effect of curcumin was correlated with decreased expression of pErk and PI3K in MDA-MB-231.