Combination chemotherapy (co-chemotherapy) is a recent strategy to reduce the toxicity effect and increase the effectivity of chemotherapeutic agent, such as Doxorubicin (Dox). Caesalpinia sappan L. are potential to be developed as co-chemoterapeutic agents due to its strong cytotoxicity toward several breast cancer cells. The purpose of this research is to observe the cytotoxicity of Brazilein containing fraction (BCF) in single and its combination with doxorubicin on T47D cells. BCF was obtained by fractionation using chloroform:ethyl acetate (40:60 v/v) as mobile phase. Molecular docking results showed that Brazilein and Brazilin interacted with Bcl-2 with different binding properties. Based on MTT assay, Dox and BCF performed potent cytotoxicity with IC50 value of 403 nM and 68 μg/mL, respectively. BCF increased the cytotoxicity of Dox and performed synergism with CI value <1 and decreased possible toxicity with DRI value>1. Under Annexin V PI staining Flowcytometry, BCF in single and its combination with doxorubicin induced apoptosis. In conclusion, single treatment of BCF and its combination with Dox performed cytotoxic effect and induced apoptosis on T47D cell lines.Keywords: Brazilein containing fraction, Doxorubicin, Co-chemoteraphy, Apoptosis, T47D cells

Anticancer activity of secang's heartwood (Caesalpinia sappan L.) is based on its main compound: brazilin and brazilein. Brazilin, brazilein, and other compounds such as caesalpiniaphenol can affect proteins that have a role in apoptosis. In this study, we observed cytotoxic activity of fraction containing brazilein (FCB) alone or in combination with chemotherapeutic agent, cisplatin and the ability of the combination to induce apoptosis in T47D breast cancer cell lines. Cytotoxicity assay was determined using MTT assay, whereas the detection apoptosis induction was conducted using flow cytometry using Annexin-V and propidium iodide. FCB and cisplatin showed cytotoxic effect on T47D cells with IC50 value of 68 µg/mL and 16 µM, respectively. Combination of FCB and cisplatin result synergistic combination at the concentration ratio of 1/2 IC50 with CI value of 0.66. Its combination also able to induce apoptosis on T47D cell population 13% larger than the single treatment. Based on this study, we conclude that FCB is able to enhance the cytotoxic effects of cisplatin by inducing apoptosis.

The usage of doxorubicin (DOX) as an anticancer drug in cancer patient may cause several side effects. One of that is cardiotoxicity by inducing the expression of nitric oxide synthase which may release nitric oxide (NO) resulting reactive oxygen species (ROS) in the cardiac. DOX needs to be combined with antioxidant since it could supressed ROS in the cardiac and reduce cardiomyopathy. Kelor (Moringa oleifera) is known as the source of antioxidant. This study aim to observe the treatment effects of ethanolic extract of kelor (EEK) on histopathology profile and concentration of NO in rats cardiac. The result from the hematoxylin-eosin staining showed that EEK improved the histopathology profile of rats' cardiac. Compared with the DOX-only treatment, the structure of cardiac muscle cells treated by ethanolic extract of kelor is more well-arranged and the cells' nucleus still visible. Concentration of NO was measured by cardiac puncture method. The result showed that the concentration of NO was decrease in line with increasing dose levels of EEK in combination with DOX. But at rats only given with EEK, the concentration of NO is quite high. In conclusion, EEK could be a cochemotherapy agent by reducing the cardiotoxicity effect of DOX.

Effective and selective chemoterapeutic and chemopreventive agent is needed to cure breast and cervical cancers. One of the potential natural material is mangosteen peel (Garcinia mangostana). In this study, we observed cytotoxic effect of ethanolic extract of mangosteen peel (EMP) on HeLa cells line and T47D cells line. The cytotoxic effect was determined using MTT assay.EMP showed cytotoxic effect on T47D cells and HeLa cells with IC50 values of 2.07 μg/ml and 10.58 µg/ml respectively. Molecular docking simulation was done to predict the molecular mechanism of active compund in mangosteen peel extract, α-mangostin, in NFқB pathway which is one of the potential pathway to induce cytotoxicity on T47D and HeLa cells. Docking was done using PLANTS software and the binding score between α-mangostin and proteasom is -78,12, whereas the binding score between α-mangostin and IKK is -86.84. These results showed the possiblity mechanism of mangostin peel extract containing α-mangostin inhibits IKK activation in NFқB pathway. Based on this study, we conclude that mangosteen peel extract is potential to be developed as chemopreventive agent toward cervical and breast cancers.Keywords: Mangosteen peel (Garcinia mangostana), cytotoxic, T47D cells, HeLa cells, NFқB

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.