# Antitumor Effects of _Cannabis sativa_ Bioactive Compounds on Colorectal Carcinogenesis
## 3 Bioactive Compounds in the Prevention and Treatment of Colorectal Cancer
### Effects of Cannabis sativa Extracts on CRC  
Interactions between terpen/ terpenoids and cannabinoids may intensify their pharmacological effects. In reality, there is growing evidence that these substances interact more favorably when used in combination than when used alone. This is known as the \"entourage effect\" in modern parlance, an effect attributed to cannabis's medical properties [43]. Although little explored, several _C. sativa_ extracts rich in cannabinoids and terpen have been claimed to exert positive effects to fight CRC (Table 4). \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Extraction Method** & **Biactive Compounds** & **Cell Line/Animal Model** & **Doses** & **Cancer-Associated Mechanisms** & **Effects on CRC** & **Refs. ** \\ \hline \multirow{6}{*}{SFE-CO\({}_{2}\)} & CBD (\(\mathbf{\tau}\)), \(\Delta^{3}\)-THC, & HCT116 and DLD-1 & HCT116 and DLD-1 & In vitro: 0.3-5 uM & Proliferation & In vitro: \(\mathbf{\tau}\) proliferation \\  & CBG, CBDV, CBDA, & A/Mutelov LR mice & In vivo10 mg/kg (AOM) & Tumor growth & In vivo: \(\mathbf{\tau}\) ACP, polyps, tumor & [87] \\  & CBN & (Core: HCT116) & 5 mg/kg (Aen) & formation, volume & \\ \cline{2-6}  & \multirow{2}{*}{ND} & In vitro 1.2, 3, and & Cell survival & \(\mathbf{\tau}\) cell viability (4 ug/mL), colony & \\  & & 4 ug/mL & Proliferation & formation, cyclin 21, CDN, Rd2; & [88] \\  & & Mice (Core: CT26) & In vivo 25, 5, and & Apoptosis & \(\mathbf{\tau}\) CG/1 GB/2 smears, apoptosis & \\  & & 10 mg/kg & Metastasis & (4 ug/mL), cleaved caspase-3 and PARP & \\ \hline \multirow{6}{*}{EOH extract} & \(\mathbf{\tau}\)s, \(\Delta^{3}\)-THC and CBD & \multirow{2}{*}{CACO-2 and HT-29} & \multirow{2}{*}{0.24–500 ug/mL} & \multirow{2}{*}{Cell survival} & \multirow{2}{*}{\(\mathbf{\tau}\) positive selective cytotoxicity against} \\  & & & & & \\ \cline{1-1}  & \(\mathbf{\tau}\)s, Herpes & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & CBG, CBD, CBDA, CBN, & 20 ug/mL (THC-rich fraction) and 35 ug/mL & Cell survival & \(\mathbf{\tau}\) cell variation & \\ \cline{1-1}  & THCA (\%) & & (CBGA-rich fraction) & Apoptosis & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & CBG, CBD, CBDA, CBN, & & & & \\ \cline{1-1}  & CBG, THC, CBC, and & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & CHG, CBD, CBDA, CBN, & & & & \\ \cline{1-1}  & CBG, THC, CBC, and & & & & \\ \cline{1-1}  & THCA (\%) & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \hline Macration (EOH and & CBD, CBDA, THC, & & & \\ \cline{1-1}  & MeOH), Sohule, UAE & THCA, CBGA, CRC, & CACO-2 & 0.625–20 ug/mL & Cell survival & Macration EOH extract: & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \hline \hline
**\(\mathbf{\tau}\)**, Increase: \(\mathbf{\tau}\)**, decrease: AC, aberrant crypt toc, AOM, axoynethene; Rd2, B-cell lymphoma 2 CB, CDD, cannabidiol CDDA, camabidiol CDDA, camabidiol; CDG, cransabidiol CDGJanatova et al. [42] suggested that the compounds responsible for the cytotoxicity of _C. sativa_ ethanolic (EtOH) extracts in CACO-2 and HT29 cell lines were THC and CBD. However, in the same work, a specific genotype containing high concentrations of myrcene, \(\beta\)-elemene, \(\beta\)-selinene, and \(\alpha\)-bisabolol oxide positively affected the selectivity of cytotoxic activity, due to synergistic effects. In another study conducted by [PERSON] and coworkers, the authors reported an increment in cytotoxic effects of a _C. sativa_ EtOH extract in CRC cells (HCT 116, HT-29, and CACO-2) when this was combined with a THCA-rich fraction [45]. In addition to the EtOH extract, fractions obtained from it were also evaluated. The combination of a CBGA-rich fraction and a THCA-rich fraction resulted in a noticeable increase in apoptosis.