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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11
th
International Conference on
Journal of Medical Oncology and Therapeutics
|
Volume 3
Maithili A Athavale et al., J Med Oncl Ther 2018, Volume 3
MOLECULES TARGETING CANCER
STEM CELLS
Maithili A Athavale, Sandip Gavade
and
Sangeeta Srivastava
Godavari Biorefineries Ltd., Somaiya Bhavan, India
T
he aim of the present project was to synthesize novel derivatives of
diphylline glycoside of Cleistanthin A (SBGB-0001-000) and to screen
them for anticancer activity (by MTT, Soft Agar Assay) and anticancer
stem cell activity (by tumorsphere assay) on breast cancer cell lines. In all
70 novel derivatives of SBGB-0001-000 were synthesized and screened
for anticancer and anticancer stem cell activity. Out of 70, two derivatives
namely, SBGB-0001-014 and SBGB-0001-023 exhibited better anticancer
and anticancer stem cell activity compared to standard chemotherapeutic
drug Cisplatin. Since, cancer stem cells (CSCs) are subpopulation of cells
within the cancer tissues with drug resistance and metastatic properties,
these two candidates were further tested for its anticancer stem cell
activity on drug (Paclitaxel) resistant population on highly metastatic
breast cancer cell line MDAMB231 (with high number of CSCs) compared
to standard chemotherapeutic drug Cisplatin and a target drug therapy
sunitinib. Our sphere assay results indicate that the candidate molecules
have better anticancer stem cell potential, inhibiting spheres at 25 nM
compared to Cisplatin and sunitinib. In (figure 1), briefly describes that,
our in-vitro data supports the anticancer stem cell effect of two novel
candidates on breast cancer cell lines. Further, these candidates do not
exhibit any toxic effect on normal cells (peripheral blood lymphocytes)
compared to Cisplatin. The molecules show good hepatocyte stability
and have been taken further for the preclinical studies like PK-PD, MTD
and Xenograft studies.
Figure 1: Indicates that the candidate molecules SBGB-0001-014 and
SBGB-0001-023 are effective on paclitaxel treated MDAMB231 cells
compared to Cisplatin at 25 nM (0.025 µM).
Maithili A Athavale has completed her PhD from
National Institute for Research in Reproductive
Health, Mumbai University, India. She has han-
dled various Projects in Research and Develop-
ment of various Pharma companies. She has
publications in national and international jour-
nals. Currently, she is working as Senior Man-
ager R&D of Biotech Division, of Godavari Biore-
fineries Ltd. Her lab is into in-vitro screening of
many novel synthetic molecules for anticancer
and anticancer stem cell activity on breast,
prostate and oral cancer cell lines. The lab has
screened and found eight novel molecules hav-
ing potent anticancer and anticancer stem cell
activity. Two of the lead molecules have entered
preclinical studies.
maithili.athavale@somaiya.comBIOGRAPHY