Andrographolide Exhibits Anticancer Potential Against Human Colon Cancer Cells by Inducing Cell Cycle Arrest and Programmed Cell Death via Augmentation of Intracellular Reactive Oxygen Species Level.

Andrographolide, a diterpenoid lactone and a major constituent of Andrographis paniculata Nees, exhibits remarkable anticancer activity. However, the effect of andrographolide on colon cancer has not been completely elucidated yet. Thus, we investigated the chemopreventive potential of andrographolide in colon cancer HT-29 cells. The cytotoxic potential of andrographolide on HT-29 cells was determined by MTT assay, trypan blue exclusion assay, colony formation assay, and morphological analysis; and apoptotic property by DAPI and Hoechst staining, FITC-Annexin V assay, DNA fragmentation assay and caspase-3 activity assay. To elucidate andrographolide action, intracellular reactive oxygen species (ROS) level was determined by DCFDA dye; change in mitochondrial potential by Rhodamine123 and Mito Tracker Red CMXRos dye; and cell cycle modulatory property by flow cytometric analysis. Results of the study have shown that andrographolide decreased cell viability of HT-29 cells in a dose- and time-dependent manner. Furthermore, andrographolide induced apoptosis in HT-29 cells which seemed to be linked with augmented intracellular ROS level and disruption of mitochondrial membrane potential. Interestingly, andrographolide caused significant cell cycle arrest in G2/M phase at lower doses, but, in G0/G1 phase at higher doses. In summary, our results indicated that andrographolide exhibited antiproliferative and apoptotic properties against colon cancer HT-29 cells.

Glycyrrhizin induces reactive oxygen species-dependent apoptosis and cell cycle arrest at G0/G1 in HPV18+ human cervical cancer HeLa cell line.

Cervical cancer is the fourth most common cancer among women worldwide and is a major cause of morbidity and mortality. High-risk Human Papilloma Virus (mostly type 16 & 18) infection is the primary risk factor for the development of cervical carcinoma. The quest for strong, safe and cost effective natural antiproliferative agents that could reduce cervical cancer have been focussed now a day. Recently, glycyrrhizin, a triterpene glycoside (saponin) from licorice (Glycyrrhiza glabra Linn.), has been shown to exhibit potent antiproliferative and anticancer properties in a few preliminary studies. However, potential of this compound in cervical cancer has not been elucidated yet. Therefore the objective of this study was to analyze the antiproliferative and apoptotic properties of glycyrrhizin in human cervical cancer HeLa cells. Our results showed that glycyrrhizin exposure significantly reduced the cell viability of HeLa cells with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed dose-related increment in ROS production induced by glycyrrhizin. Glycyrrhizin also induced apoptosis in cervical cancer cells by exerting mitochondrial depolarization. Cell cycle study showed that glycyrrhizin induced cell cycle arrest in G0/G1 phase of cell cycle in a dose dependent manner. Thus, this study confirms the efficacy of glycyrrhizin in cervical cancer cells which could be an adjunct in the better prevention and management of cervical cancer worldwide.

Carvacrol Induces Reactive Oxygen Species (ROS)-mediated Apoptosis Along with Cell Cycle Arrest at G0/G1 in Human Prostate Cancer Cells.

Carvacrol, a major monoterpenoid phenol from Origanum and Thymus species, has been shown to exhibit antiproliferative and anticancer properties in a few recent studies. Nevertheless, detailed mechanism of the action of this compound in prostate cancer has not been elucidated yet. Therefore, in the current study, we examined the anticancer activity and mechanism of the action of carvacrol against human prostate cancer cells. It was found that the treatment of DU145 cells with carvacrol decreased cell viability in a concentration and time-dependent manner. The antiproliferative action of carvacrol leads to induction of apoptosis as confirmed by nuclear condensation, Annexin V-FITC/PI positive cells, and caspase-3 activation. In addition, carvacrol augmented reactive oxygen species generation and disruption in the mitochondrial membrane potential which has not been reported in the previous studies of carvacrol with prostate cancer. Moreover, carvacrol-induced apoptosis of prostate cancer cells was also accompanied by significant amount of growth arrest at the G0/G1 phase of the cell cycle which has also not been documented previously. To sum up, this study has established that carvacrol could be a promising chemotherapeutic agent and could have a direct practical implication and translational relevance to prostate cancer patients as Origanum consumption may retard prostate cancer progression.

How we developed a bioethics theme in an undergraduate medical curriculum.

The 5-year undergraduate medical curriculum at Aga Khan University integrates basic sciences with clinical and community health sciences. Multimodal strategies of teaching and learning, with an emphasis on problem-based learning, are utilized to equip students with knowledge, skills, behaviours, attitudes and values necessary for a high-calibre medical graduate. Bioethics teaching was introduced in the medical curriculum in 1988 and has since undergone several changes. In 2009, a multidisciplinary voluntary group began review of undergraduate bioethics teaching and invested over 350 man-hours in curricular revision. This involved formulating terminal objectives, delineating specific objectives and identifying instructional methodologies and assessment strategies appropriate for the contents of each objective. Innovative strategies were specially devised to work within the time constraints of the existing medical curriculum and importantly, to increase student interest and engagement. The new bioethics curriculum is designed to be comprehensive and robust, and strives to develop graduates who, in addition to being technically skilled and competent, are well-versed in the history and philosophy of ethics and bioethics and are ethical in their thinking and practice, especially in the context of a developing country like Pakistan where health indicators are among the worst in the region, and clinical practices are not effectively regulated to ensure quality of care.