(S)-10-hydroxycamptothecin is an inhibitor of DNAtopoisomerase I with antitumor activity.
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(S) -10-Hydroxycamptothecin (HCPT) is a TOP I (Topoisomerase I) specific inhibitor. HCPT inhibits the growth of ESCC cells in vitro and verify its anti-tumor activity in vivo by using a patient-derived xenograft (PDX) tumor model in mice. HCPT also induced DNA damage by increasing the expression of H2A.XS139. HCPT significantly decreased the proliferation and anchorage-independent growth of ESCC (Esophageal squamous cell carcinoma) cells (KYSE410, KYSE510, KYSE30, and KYSE450). Mechanistically, HCPT inhibited the G2/M phase cell cycle transition, decreased the expression of cyclin B1, and elevated p21 expression. In addition, HCPT stimulated ESCC cells apoptosis, which was associated with elevated expression of cleaved PARP, cleaved caspase-3, cleaved caspase-7, Bax, Bim, and inhibition of Bcl-2 expression. HCPT dramatically suppressed PDX tumor growth and decreased the expression of Ki-67 and TOP I and increased the level of cleaved caspase-3 and H2A.XS139 expression. HCPT inhibited ESCC growth, arrested cell cycle progression, and induced apoptosis both in vitro and in vivo via decreasing the expression and activity of TOP I enzyme[3]. HCPT may induce fibroblast apoptosis by regulating miR‑23b‑3p expression[4].(S)-10-Hydroxycamptothecin (OPT), an analog of camptothecin (CPT), was found to inhibit the growth of the mouse hepatoma BW7756, when given at 1.0 mg/kg/day for 14 days. This drug inhibited the S-Phase of the tumor cells in vivo and the S and G2/M phases in vitro[5].
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