ROR1 – a receptor tyrosine kinase – is overexpressed in CLL. Ibrutinib, a Bruton's tyrosine kinase inhibitor, is clinically effective in CLL but patients may develop resistance. We evaluated the effect of an ROR1 inhibitor, KAN0441571C, in CLL cells from six patients obtained before and after developing resistance to ibrutinib. The ROR1 inhibitor induced apoptosis in ibrutinib‐resistant CLL cells to the same degree as in ibrutinib‐sensitive cells and dephosphorylated ROR1. This was also noted in one patient who became resistant to both ibrutinib and the Bcl‐2 inhibitor venetoclax. The combination of ROR1 inhibitor and venetoclax had a synergistic apoptotic effect on ibrutinib‐resistant cells.

Metastasis is the main cause of death among brast cancer patient. Pleorotus ostreatus is known as anticancer agent that inhibits angiogenesis. Ethanolic extract of Pleorotus ostreatus (EEP) which contains lovastatin is predicted to inhibit metastatic cancer through inhibition of MMP-2 and MMP-9. The aim of this study was to determined antiproliferative and anti metastatic activity of EEPw (Ethanolic extract of wet Pleorotus ostreatus) and EEPd (Ethanolic extract of dried Pleorotus ostreatus) in 4T1 metastatic breast cancer cells line. Qualitative analysis of lovastatin was determined by thin layer chromatography (TLC) using dicloromethan and etil acetat as mobile phase and lovastatin standard. Scratch wound healing assay was used to determine migration inhition ability of EEP while MMP-9 and MMP-2 activity were analysed by gelatine zymography. Molecular docking was performed to know the interaction between lovastatin and MMP-2 & MMP-9. The result showed that EEPw and EEPd contain lovastatin which were proved by spray reaction with anisaldehid. Each of EEPw and EPPd had cytotoxic activity with IC50 760 and 400 μg/mL respectively. Both of them inhibited closure for about 50 % on 4T1 metastatic breast cancer cells line compared to control. Either EEPw or EEPd decreased MMP-9 expression level compared to control. Lovastatin had higher affinity to bond with either MMP-2 or MMP-9 than native ligand. Overall, EEP could be developed as anticancer agent which was targeted on MMP-2 and MMP-9.

Citrus hystrix D.C. (kaffir lime) peel contains several flavonoids including rutin, naringenin, hesperidin. C. hystrix peel ethanolic extract (ChEE) has shown its potency as cardioprotector agent in chemotherapy. However, there are limitations to the utilization of ChEE due to its poor water solubility and low oral bioavailability. Accordingly, selfmicroemulsifying drug delivery system (SMEDDS) formulations were developed to improve the oral absorption of flavonoids. Tween 80, Corn oil, and propylene glicol (5:1:1ml) were combined to form ChEE-SMEDDS. The present study is to evaluated ChEE-SMEDDS for their physicochemical properties and in vivo using combination with doxorubicin to see blood serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitrit oxide (NO) activity and also cardio-hepato-histopathology of female Sprague Dawley rats. The results showed that ChEE-SMEDDS repaired cardio-hepato-histopathology profile of doxorubicininduced rats, but did not reduce serum activity of NO, ALT and AST. These results indicated that ChEE-SMEDDS has potency to be developed and improved as cardio-hepato-protector agent in chemotherapy.

DNA damage usually happens due to the several chemical materials that induce genotoxic effect in normal cells. Cinnamon essential oil (CEO), which contains cinnamaldehyde as its major compound, has been reported to possess antioxidant activity to prevent DNA damage. The aim of this study is to evaluate the genotoxic and cytotoxic effect of CEO on doxorubicin-induced Chinese Hamster Ovary (CHO-K1) cells. The cytotoxic effect of CEO was determined by MTT assay with the parameter of IC50 while the genotoxic effect was carried out by micronucleus (MN) assay by using acridine orange fluorescent staining with the parameter of MN/1000 cells reduction number. Based on MTT assay, CEO showed cytotoxic activity with the IC50 value of 30 μg/mL and for MN assay, 3 μg/mL ( 1 /10 IC50) of CEO decreased the percentage of micronucleus per 1000 cells up to 94.55%. Thus, the result can be summarized that CEO does not induce genotoxic and has the potency to prevent DNA damage caused by doxorubicin on CHO-K1 cells.