Effects of isocamptothecin, a novel camptothecin analogue, on proliferation, apoptosis and telomerase activity in HaCaT cells

Abstract

Camptothecin is a topoisomerase I inhibitor with definite anti-psoriatic effect. As it is limited in clinical application because of serious side effects and toxicity, many researchers are striving hard to develop derivatives or analogues of camptothecin with higher effects and less toxicity. To explore the anti-psoriatic potential of isocamptothecin, a novel camptothecin analogue, its effects on proliferation, apoptosis and telomerase activity were investigated in the human keratinocyte cell line HaCaT. Incubation with isocamptothecin resulted in a time- and concentration-dependent inhibition of HaCaT cell proliferation. However, isocamptothecin showed larger inhibitory concentration at 50% than camptothecin, suggesting far less cytotoxicity. In addition, isocamptothecin induced apoptosis in a concentration-dependent manner and induced typical morphologic features of apoptosis in HaCaT cells. Moreover, isocamptothecin downregulated the telomerase activity of HaCaT cells not only at concentrations of apoptosis induction but also at concentration insufficient to induce apoptosis, providing additional mechanisms that further account for its ability to inhibit keratinocytes proliferation and induce apoptosis. These results indicate that isocamptothecin possesses similar effects on keratinocytes with camptothecin, but shows far less cytotoxicity, it may probably become a promising agent for psoriasis therapy.

Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin

“…However, slight irregularities in the plasma membranes and microfilaments of microvilli were observed for the camptothecin dosed alone (Figure 9, Figure S20, supplementary information). Disruption of microvilli has been previously noted in cells treated with camptothecin (Bredholt et al, 2009; Lin et al, 2008). When the camptothecin was dosed with the PAMAM dendrimers-G4.0 and G3.5, the microvilli did not show swelling and the microfilaments inside the microvilli were well organized (Figure 9, Figure S21-24, supplementary information)).…”

Effect of Topical Application of Black Seed Oil on Imiquimod‐Induced Psoriasis‐like Lesions in the Thin Skin of Adult Male Albino Rats

“…In spite of the fact that psoriasis is thought to be a Th1 disorder, the occurrence of psoriasis does not differ between immunodeficiency virus‐infected patients and the general community. Subsequently, epidermal changes may mark the start of skin lesions in psoriasis; as such, prevention of keratinocyte multiplication might be a useful strategy to combat this disease and might be considered as a promising target of anti‐psoriatic strategies (Lin et al, ).…”

1,4-dihydroxy-2-naphthoic Acid Induces Apoptosis in Human Keratinocyte: Potential Application for Psoriasis Treatment

“…Therefore, it is believed that epidermal alterations may account for the initiation of skin lesions in psoriasis and thus restoring hyperproliferative keratinocytes to normal would be beneficial in this disease. Particularly, inhibition of keratinocytes proliferation and induction of keratinocyte apoptosis have long been considered as targets of antipsoriatic strategies [31], and the discovery of new antiproliferative and keratinocyte differentiation-modulating agents remains a worthy aspect in psoriasis research nowadays.…”